Antibiotic Prescribing in Podiatric Medicine

January 24th, 2012 by Warren S. Joseph DPM FIDSA

I recently came across some fascinating data which breaks down the number of outpatient prescriptions written by podiatrists for all different classes of drug in 2010.  Unlike various surveys that have been done over the years by different magazines, this is hard data based on the actual number of scripts.  I would like to comment on some findings I find interesting in the use of antibiotics. 

Antibiotics were the third most commonly prescribed class of drug following narcotic analgesics and NSAIDs with over 1.6 million scripts written.  This is followed closely by antifungals at about 1.4 mil prescriptions. (Perhaps a topic for a future post?).  I don’t think it would come as any surprise that cephalexin is the most prescribed (530,000) and is actually the second most common drug written by DPMs.  The number two most common antibiotic would also probably not come as a big surprise, amoxicillin/clavulanic acid (Augmentin) down the line a bit at number 15 (177K).  Although amox/clav is a good antibiotic with a favorable spectrum for more complicated lower extremity infections, it is probably a bit unnecessarily broad spectrum for everyday use. I have started to limit my use of this drug after I personally had to take it for an endodontic problem.  First, the 875mg is an amazingly large pill which is not easy to swallow.  Also, I always knew that the drug could be a bit hard on the GI tract and I knew to take it with food and a full glass of water.  Despite those precautions, about 20 minutes after I took each dose, I found my stomach wanting to jump out of my abdomen!  It is true what they say about how a physician can change his way of treating folks after he becomes a patient. 

The third most commonly used antibiotic is trimethoprim/sulfamethoxazole (Bactrim/Septra) with 117K Rx’s.  Not surprisingly, this drug’s use has increased dramatically over the past few years with as few as 34K scripts only 2 years before, a stunning increase in such a short period of time.  Probably all of this usage is for the presumptive treatment of MRSA even before cultures have been returned.  I have said it before; I will repeat is again here, I do NOT like to routinely use this drug.  There are reasons this drug was rarely used before the MRSA epidemic we find ourselves facing.  Although broad spectrum, generic and inexpensive it is not benign. Toxicities range from life threatening skin reactions, such as Stevens-Johnson syndrome to renal, neurologic, psychiatric and hematologic problems, not to mention sulfa allergy, drug-drug interactions with other sulfa based drugs and the inability to use in patients with a G6PD deficiency (and, YES, you will see this as I recently did in a patient with a multi-drug resistant Enterobacter cloacae where the ONLY drug to which the organism was reported as susceptible was TMP/SMX).  Because of the lack of studies showing clinical efficacy against MRSA there is also some question as to how it should be dosed for MRSA infections.  It has been suggested that the usual 1DS b.i.d. is insufficient and that should be routinely increased to 2DS b.i.d. thus potentially increasing the rate of adverse events even further.  That is not to say I don’t use TMP/SMX, I just don’t routinely give it to every patient empirically to cover MRSA or even with a positive MRSA culture unless there are other reasons to use it, such as a mixed infection where the use of one drug obviates the need for combination therapy. 

I often get asked the question; “if not TMP/SMX, then what oral antibiotic you using for your MRSA cases”.  That depends on severity.  For my more mild infections where most of you are probably using TMP/SMX, I much prefer doxycycline 100mg q12h.  Minocycline can also be used.  I find that there is more data to support their use and they are well tolerated even for longer courses of therapy such as in osteomyelitis.  Interestingly, NEITHER of these antibiotics is found in the top 60 drugs written by podiatrists.  I would like to see that change.

The next most commonly prescribed antibiotics drive me crazy!  They are ciprofloxacin at 101K followed by levofloxacin at 75K.  Those who have heard me lecture know that I have been preaching avoidance of quinolones, particularly ciprofloxacin since it was first released and people were sold a “bill of goods” about how broad spectrum it was and how wonderfully it penetrated bone.  As time has gone on, my feelings have only intensified. If I am going to use a quinolone, it is levofloxacin rather than ciprofloxacin because of its better gram positive activity and the once daily dosing.  The only time I see a use for ciprofloxacin is for a documented Pseudomonas infection, something that is extremely rare in lower extremity infections (see post on “Pseudomonaphobia”).   Even then, there is no data to suggest that levofloxacin would not be equally efficacious.  Another quinolone, moxifloxacin, has the advantage of better anaerobic coverage in the case of a diabetic foot infection.  My quinolone usage is on a significant decline.  As a class, these drugs can potentiate the development of MRSA infections, have significant toxicities and, probably most importantly, have been implicated in the development of multi-drug resistant (MDRO) gram negative infections.  In fact, at Roxborough a recent antibiogram shows only about 50% of our E. coli still susceptible to ciprofloxaxin.  Furthermore, I have been noticing lately that every patient who gets sent out on a quinolone invariably returns to the hospital but now with an organism resistant to the entire class.  PLEASE, use these drugs sparingly and only when appropriate!!

The final drug on the list I would like to discuss is amoxicillin, currently being prescribed 28,000 times per year.  This, I just don’t understand at all.  Frankly, I don’t think I have ever written for straight amoxicillin nor do I see any reason to ever do so.  Perhaps, if the patient presents with an infection solely caused by Enterococcus or a straight Streptococcal infection, then it may be a reasonable choice but these are extremely rare and I seriously doubt they are occurring 28K times.  This leads me to believe that there is some inappropriate use of amoxicillin in the profession.  Please remember that this drug is not beta-lactamase stable and is therefore ineffective against essentially all clinically relevant S. aureus

These data reveals some interesting information about how lower extremity infections are being treated.  Overall, I find the usage pretty reasonable however, when it comes to what I perceive as an overuse of TMP/SMX, quinolones and amoxicillin, we can always do better.

Posted in Antibiotics, Diabetic Foot, Infections, MRSA | 1 Comment »

Bacteria and Social Networking

January 9th, 2012 by Warren S. Joseph DPM FIDSA

A few weeks ago my old Podiatric College roommate sent me a link to a fascinating YouTube video.  I then sent it to a few friends who, in turn, posted it on a few other blogs so it has become a minor viral (or should I say “bacterial”) success.  This lecture, by Professor Eshal Ben-Jacob of Tel Aviv University, covers aspects of bacterial communication and their “social interactions” as regulated by various stimuli.  It is an utterly fascinating subject presented in a clear, understandable manner with incredible videos and photographs.  This work has major implications in the way bacteria become pathogenic, are currently treated and some future directions that could be considered.  Just as a “heads-up” it will take a commitment of time from you, the viewer, as the lecture is an hour long but please don’t let that keep you from viewing it in its entirety.  It is absolutely worth it.  http://www.youtube.com/watch?v=yJpi8SnFXHs

Posted in infection control, Infections, Wounds | No Comments »

A New Review of Antibiotic Therapy for Osteomyelitis

January 4th, 2012 by Warren S. Joseph DPM FIDSA

I wish all of my readers a healthy, happy and prosperous 2012.  With this post I am trying something a bit different.  In the past I usually waited to put up a post until I come up with an “ah ha” moment on something I have seen, heard or read about which I then pontificate on this site.  These could occur only days apart, but usually it was a much longer time period leading to relatively infrequent additions to the blog.  My “resolution” for 2012 is to try to put up more frequent, quick hits where I don’t have as much to write and you don’t have as much to read.  That’s not to say that I won’t still post the occasional tome on a particular topic.  Sometimes, I just have to vent!  I have one coming up shortly on antibiotic usage in podiatric medicine…just a heads up.

A recent paper has been published in Clinical Infectious Diseases by Brad Spellberg at UCLA and Ben Lipsky at the Puget Sound VA titled Systemic Antibiotic Therapy for Chronic Osteomyelitis in Adults (http://www.ncbi.nlm.nih.gov/pubmed?term=Spellberg%20B%20AND%20Lipsky%20BA).  I consider it a MUST READ for followers of this site.  This excellent review covers topics including the pharmacology of osteo therapy (i.e. parenteral vs. oral, bone penetration), animal models of osteo, human non-randomized clinical trials and randomized clinical trials.  It is THOROUGH yet quite readable at only 11 pages (there are, however, 172 references!) with 5 tables outlining all of the studies discussed. 

The authors arrive at 4 conclusions which I quote directly from the paper:

1.  “Oral antibiotic therapy with highly bioavailable agents is an acceptable alternative to parenteral therapy.”

2.   “Adding rifampin to a variety of antibiotic regimens has been shown to improve cure rates”

3.   “Clinicians must individualize the duration of antibiotic therapy based on the patient’s clinical and radiographic response…”

4.   “Surgical resection of necrotic and infected bone, in conjunction with antibiotic therapy, appears to increase the cure rate of chronic osteomyelitis. However, not all cases of chronic osteomyelitis require surgical debridement for cure, and we need studies to clarify which may and which may not.”

None of these conclusions should come as a surprise to regular readers of this blog or those who have heard me lecture on the topic, as I have discussed these very points in the past.  Dr. Lipsky and I collaborate frequently and I find it almost frightening how often we agree.  In this one paper he and Dr. Spellberg have eloquently laid out all of the evidence supporting these positions.  If I have said it once, I have said it a thousand times…We MUST rethink the universally pervasive dogma of 4-6 weeks of IV antibiotic therapy for osteomyelitis based on the best available evidence!

Posted in Antibiotics, Diabetic Foot, Infections, Osteomyelitis | No Comments »

SCIP Surgical Prophylaxis?

November 13th, 2011 by Warren S. Joseph DPM FIDSA

One of the most frequent questions I am used to be asked is about when antibiotic prophylaxis should be used in performing foot and ankle surgery.  I have an entire lecture on this topic where I go through the data, or lack thereof, on the subject and suggest the clinical situations where prophy has traditionally been utilized (i.e. surgery longer than 2 hours, trauma surgery, immunocompromised hosts, etc).  More and more the question posed to me has become: “Warren, my hospital requires me to use prophylactic antibiotics even when I don’t feel they are necessary.  They have actually threatened to take away my surgical privileges if I don’t use them.  What can I do about that?”  Unfortunately, the answer is…not much.

Why is this happening?  What has changed?  In my opinion there are two main reasons we have come to be in this situation. 1) The Surgical Care Improvement Project (SCIP) 2) Changes in CMS guidelines that will not reimburse a hospital for a re-admission for a nosocomial infection. 

Point #2 is fairly self explanatory.  Hospitals don’t get paid if a patient is readmitted with a diagnosis of a nosocomial post operative infection.  Therefore, they need to try everything in their power to prove that any infection that does occur is not their fault and they did everything possible to prevent that infection.  Chief amongst these is demanding prophylactic antibiotics be given to everyone undergoing surgery.  Then, when the patient gets infected they can always claim that the infection was community acquired and not nosocomial.   

Point #1, SCIP, may not be as well known by the average lower extremity surgeon and is a bit more complicated.  Back in 2005 a national initiative was developed to attempt to reduce post operative complication rates by 25% in a 5 year period.  A set if 20 measures were developed, 9 are publicly reportable, 6 of which focused specifically on postoperative infection prevention.  4 of these are directly relatable to lower extremity work.  These include:

1.  INF-1:  Patients need to receive prophylactic antibiotics within one hour prior to surgical incision or 2 hours if using vancomycin.

2.  INF-2: Patients receive prophylactic antibiotics recommended for their specific surgical procedure

3.  INF-3: Patients prophylactic antibiotics are discontinued within 24 hours after surgical end time

4.  INF-6: Surgery patients should have appropriate hair removal with a clippers or depilatory, if at all (no razors)

I think that all readers would agree that this is a lofty and worthy goal.  The program is “voluntary” although CMS reduces hospital reimbursement by 2% if they fail to report performance on the various measures.  Probably, for this reason, the participation rate is around 95% of all hospitals.  Now the bad news…IT MAY NOT BE WORKING! 

In the June 23, 2010 issue of the Journal of the American Medical Association, Stulberg and colleagues published a retrospective cohort analysis of over 400,000 patient discharges between 2006 and 2008 (PubMed Link: http://www.ncbi.nlm.nih.gov/pubmed?term=Stulberg%20JJ%20AND%20SCIP ).  They found that when the measures were taken all together in an “all or none” infection prevention score, there was a lower probability of developing a post operative infection.  However, adherence to any individual measure (such as the use of prophylactic antibiotics) was NOT associated with a significantly lower probability of infection.

There are some other interesting tidbits to take away from this study.  The category of “Neck, Back or Extremity Surgery” presented with the overall lowest rate of post operative infection at only 0.19%.  Also, in fairness, although not reaching a level of statistical significance, the use of prophy did decrease the overall risk of infection from 21.0 to 7.5 per 1000 discharges (unfortunately, this was not broken out by procedure type).  I would also point out that the SCIP protocols do not demand all patients receive antibiotics, just that the “recommended” antibiotic, according to nationally accepted guidelines, is given.  Somehow this seems to have been morphed into a requirement to administer them.

So what does this all mean to the lower extremity surgeon?  The risk of infection for our surgery remains very low, somewhere probably well below 1.0%.  In the largest study of its type, published in JFAS in 2004, Zgonis retrospectively looked at charts from 555 patients undergoing elective foot and ankle surgery and found no statistically significant difference in infection rate in the group that received prophy vs. those who did not (PubMed link: http://www.ncbi.nlm.nih.gov/pubmed/15057856 ).  The bottom line is that prophylactic antibiotic use is probably not medically necessary in these patients.  Unfortunately, unless you are ready to really “battle City Hall”, from a practical standpoint you are going to continue to be coerced into using antibiotics you suspect are not beneficial. 

I find this all rather ironic.  In an environment where hospitals are being required (at the risk of the same possible decrease in reimbursement) to have Antimicrobial Stewardship programs to effectively decrease antibiotic usage, physicians are being told by those same administrations that they need to use antibiotics that are probably not necessary.

Post operative infection

 

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New FDA Safety Communication on Linezolid and Psychiatric Medications

October 26th, 2011 by Warren S. Joseph DPM FIDSA

One of the trickiest issues in prescribing linezolid for patients with MRSA or VRE infections is the potential for a drug-drug interaction, leading to serotonin syndrome (SS), with various serotonergic psychiatric medications.  It seems that every pharmacy computer system in the world goes crazy with warnings when you attempt to write for this antibiotic while the patient is on these meds.  The package insert for linezolid states that it is contraindicated to use linezolid in combination with SSRIs, tricyclic antidepressents, triptans, meperidine or buspirone “Unless patients are carefully observed for signs/or symptoms of serotonin syndrome…”

On October 20 the FDA updated information on this potential interaction. (http://www.fda.gov/Drugs/DrugSafety/ucm276251.htm).  They are now saying that not all serotonergic psychiatric drugs have an equal capacity to cause SS.  Most patients reported to the FDA with SS were taking SSRIs or serotonin norepinephrine reuptake inhibitors (SNRI).  They report that it is currently unknown whether co-administration of linezolid in patients taking other psychiatric drugs carries a comparable risk.  SSRIs and SNRIs that have been implicated include the following drugs commonly seen in lower extremity practice; paroxetine (Paxil, Paxil CR), fluoxetine (Prozac), citalopram (Celexa), escitalopram (Lexapro), venlafaxine (Effexor) and duloxetine (Cymbalta).  The FDA lists the risk as “unclear” in tricyclic antidepressants, MAO inhibitors and a number of other psychiatric drugs.   The reader is directed to the above link for the full list. 

What does all of this mean to the practicing provider?  A review of the literature reveals a number of isolated case reports of SS in patients receiving linezolid.  There are few large patient series reported.  In 2006 Taylor et al from the Mayo Clinic reported on a retrospective review of 52 patients who received concomitant linezolid and SSRI therapy while 20 received therapy within 14 days of each other but not concomitantly ( http://www.ncbi.nlm.nih.gov/pubmed/16779744).  They found only 2 patients (3%) had a “high probability of SS”.    They concluded that “…if the clinical situation warrants use of linezolid in a patient receiving an SSRI, linezolid may be used concomitantly with SSRIs, without a 14-day washout perioed and with careful monitoring (my italics to show this is in line with the package insert) for signs and symptoms of SS.” 

As with any antibiotic selection there is a risk-benefit ratio that should be weighed.  In a patient who NEEDS linezolid, even if they are on a SSRI, they can still receive the drug, as long as they are monitored for signs of SS.  What the new FDA information says is that not all of these psychiatric drugs are “created equal” and a blanket pharmacy warning should be carefully evaluated. 

(Disclaimer: I am a consultant/speaker for Pfizer and have received honoraria)

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Literature Update – Antimicrobial Agents and Chemotherapy, Sept, 2011

September 7th, 2011 by Warren S. Joseph DPM FIDSA

As I have mentioned in a previous post there are a number of journals I follow to stay abreast of developments in the ID, microbiology and antibiotic world.  For updates on the latest in antibiotic development from pre-clinical through clinical testing no journal beats the American Society of Microbiology’s Antimicrobial Agents and Chemotherapy (http://asm.org/).  Just to give a taste of how relevant this publication can be to those of us treating lower extremity infections, in the current September 2011 issue of AAC there at least 5 papers that present useful information.  In this “Literature Update” I will list these manuscripts, give the PubMed link to their Abstracts, and give a summary of what the authors reported.

Richter SS, et.al. Activity of ceftaroline and epidemiologic trends in S. aureus isolates collected from 43 medical centers in the United States in 2009.   (http://www.ncbi.nlm.nih.gov/pubmed?term=Richter%20SS%20ceftaroline).  The authors looked at the results of a nationwide S. aureus surveillance program collecting clinical isolates from 43 medical centers throughout the US during 2009.  Hospitals each submitted 100 consecutive isolates to a reference laboratory for in depth testing including PCR to determine the exact strain and presence of absence of Panton-Valentine leukocidin (PVL) production along with microbroth dilution testing to determine susceptibility to a broad range of antibiotics.  4,210 isolates were tested. The so-called “Community associated” strains, genotype USA300 and USA100, constituted almost 40% of all isolates (MRSA and MSSA) with the USA300 being the most commonly found single strain of MRSA at 50.6% of isolates.  As one would expect it was, by far, the most commonly isolated from wound and abscess specimens and therefore continues to be the type of most importance to those of us treating the lower extremity.  Turning to the question of antibiotic susceptibility for the USA300 strains resistance rates were as follows: erythromycin, 90.9%; levofloxacin, 49.1%; clindamycin, 7.6%; tetracycline, 3.3%; trimethoprim/sulfa, 0.8%; daptomycin 0.4%; ceftaroline and linezolid, 0%. 

Wiskirchen DE, et.al. Determination of tissue penetration and pharmacokinetics of linezolid in patients with diabetic foot infection using in vivo microdialysis. (http://www.ncbi.nlm.nih.gov/pubmed/21709078).  I have been an unabashed fan of the work by David Nicolau and his Center for Anti-infective Research and Development at Hartford Hospital.  In particular, their work in the area of microdialysis (“micro-D”) to determine tissue penetration in both bone and soft tissue has been, in my mind, groundbreaking.  It is a standardized proven methodology for determining antibiotic levels in different tissues, something that has been sorely lacking.  In this paper they turn their catheters on to the study of linezolid levels in infected diabetic foot wounds.  The micro-D technique is described in detail in the paper but basically a catheter is inserted into the tissue in question and the catheters are continuously perfused with Lactated Ringer’s. Dialysate samples are then collected from the catheters and antibiotic levels are measured. In this study the catheters were placed in uninfected thigh tissue and within 10cm of the infected foot wound.  9 patients were evaluated.  The patients were brought to steady state on IV linezolid and serum samples were collected at the same time as catheter samples to compare the two.  Again, the results of this elegant study should be read in their entirety but the conclusion was that “…linezolid penetrated equally well into both healthy thigh tissue and infected wound tissue as demonstrated by the tissue penetration ratios (AUCtissue/AUCplasma) of 1.42 in thigh tissue and 1.27 in wound tissue.”   There was fairly wide variation between patients which is not at all surprising considering the normal differences we see in this population.  Interestingly, these numbers where higher than an earlier study done in normal volunteers.

Gomez J, et.al. Linezolid plus rifampin as a salvage therapy in prosthetic join infections treated without removing the implant. (http://www.ncbi.nlm.nih.gov/pubmed/21690277) In this study out of Spain the authors evaluated 161 hip and knee prosthetic joint infections which had failed on previous therapies (teicoplanin, ciprofloxacin or TMP/SMX with rifampin).  These patients were switched to linezolid plus rifampin, 600 mg po q12h plus 300 mg po q12h, without removing the implant.  Cultures were positive in 28 cases.  Interestingly, methicillin resistant S. epidermidis was found in 22 while MRSA was found in 6 cases.  The mean duration of therapy was 80.2 days (range 21-180).  At 2 years of follow-up the remission rate was 69.4%.  A large amount of purulent drainage at the initiation of the therapy was a predictor of failure.  3 patients developed thrombocytopenia and 3 developed anemia but the linezolid did not have to be discontinued in any of these cases.  This study, although perhaps not directly applicable to daily practice is worth reading for a number of reasons.  With all of the publicity given to MRSA we sometimes forget the role coagulase negative Staph can cause in prosthetic joint infections.  Also, there has been concern for giving prolonged courses of linezolid because of the risk for myelosuppression. As this, the linezolid package insert, and other studies have demonstrated it certainly can be an issue but it rarely causes a need for discontinuation of therapy.  Upon discontinuation the changes are reversible.  Finally, as I have discussed in a previous post, it is possible that rifampin should be considered as adjunctive therapy when treating bone and joint infections caused by resistant Staph.   

Usually fungal articles in AAC deal with systemic infections.  It is rather uncommon to find articles about tinea pedis and onychomycosis.  This month there were actually 2!  Both are brief reports.

Carrillo-Muñoz AJ, et.al. Sertaconazole nitrate shows fungicidal and fungistatic activities against T. rubrum, t. mentagrophytes and E. floccosum, causative agents of tinea pedis. (http://www.ncbi.nlm.nih.gov/pubmed/21746955) In this brief in vitro study 150 clinical isolates of dermatophytes were tested for fungicidal and fungistatic activity using sertaconazole (Ertaczo).  The testing showed fungicidal activity against all three organisms with better activity against T. rubrum and E. floccosum than against T. mentagrophytes.  According to the authors this result was important since, prior to this study; the only fungicidal data for this drug was limited to two strains of T. mentagrophytes.  Their conclusion was that, although the clinical advantage of fungicidal over fungistatic activity for tinea pedis products remains unclear, “these dual fungicidal and fungistatic activities of sertaconazole are consistent with its efficacy against tinea pedis in randomized, placebo-controlled clinical trials”.  

Krishna G, et.al. Determination of posaconazole levels in toenails of adults with onychomycosis following oral treatment with four regimens of posaconazole for 12 or 24 weeks.  (http://www.ncbi.nlm.nih.gov/pubmed/21746944)  In this pharmacokinetic data reporting from a phase 2 clinical trial, patients were treated with oral posaconazole (100, 200, 400mg) once daily for 24 weeks or 400 qd for 12 weeks.  Drug concentrations from both nail clippings and plasma were collected.  118 patients completed treatment. In the hallux posaconazole was detected as early as 2 weeks in the 200 and 400 mg dose groups.  The levels were dose related and continued to rise even after discontinuation of the drug.  Plasma levels reached steady state and stayed there, declining once the drug was stopped.  The authors opined that posaconazole remained high in the nail after treatment was discontinued “…probably because posaconazole accumulated in the nail matrix via systemic absorption during treatment.  As the nail plate grew out, posaconazole was incorporated into the nail plate moving away from the nail fold, where it persisited at the distal end of the nail plate.” You may now ask yourself “Why have I never heard about this drug?”  Posaconazole was being developed by Schering-Plough for possible oral use in onychomycosis.  SP was bought by Merck and priorities in drug portfolios change.  I am currently uncertain about the fate of this drug’s future development.

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Why I Don’t Eat Raw Oysters

August 15th, 2011 by Warren S. Joseph DPM FIDSA

The more I read the infectious disease literature the more my diet becomes limited. It seems that new reports of contaminated food are published regularly.  It gets to a point where you don’t know what you should and should not eat!  I have always been wary of raw foods and rarely eat sushi especially after an article was published in Clinical Infectious Diseases a number of years ago complete with pictures of the worm coughed up by a patient who ate salmon sushi (I apologize for not being able to find the reference and to those of you who love to eat sushi, it’s just not for me). But even cooked foods I thought would be safe are suspect.  Take for example the report I read back in 1998 of a botulism outbreak from baked potatoes that were wrapped in foil. (PubMed: http://www.ncbi.nlm.nih.gov/pubmed?term=baked%20potato%20food%20poisoning ). More recently there has been the incredibly deadly Shiga toxin producing E. coli outbreak centered in Hamburg and Lubeck, Germany, the mystery fortunately solved one week before my wife and I visited both of those wonderful cities on vacation.  If these examples weren’t enough to cause consternation, consider two papers published in the July 15, 2011 issue of Journal of Infectious Diseases. This first is an Editorial Commentary by Daniel Bausch: Ebola virus as a foodborne pathogen? Cause for consideration, but not panic.   EBOLA VIRUS!!??  That deadly organisms from Africa that kills 90% of all whom it infects?  In food?  Fortunately, there really is no reason for panic.  The author discusses how a variant of the virus, known as the Reston EBOV, which is not known to be pathogenic in humans, has been found in pigs in the Philippines…but, still…

A second article in the same issue by Behravesh, et al; Deaths Associated with bacterial pathogens transmitted commonly through food, is an analysis of the Foodborne Diseases Active Surveillance Network (FoodNet). Fortunately, death from foodborne illness remains relatively rare, reported at just 0.5% of cases with most being in adults >65.  Salmonella and Listeria were the most common causes followed closely by Vibrio, which brings us to the following:

I have always been fascinated by infections caused by various Vibrio species found primarily in raw oysters.  Early in my ID career I attended the Interscience Conference on Antimicrobial Agents and Chemotherapy (ICAAC) one of the great antibiotic and microbiology meetings, when it was held in New Orleans in 1986.  3 years later a study was published by Lowry, et al, in Journal of Infectious Diseases which reported on Vibrio gastroenteritis in attendees of the meeting who ingested raw oysters (PubMed: http://www.ncbi.nlm.nih.gov/pubmed/2584764). The authors found that 12% of respondents reported diarrhea and the risk was significantly higher in those who ate raw or cooked oysters. Furthermore, they found that cultures of raw and cooked seafood at local restaurants yielded 5 different species of Vibrio!  Searching of PubMed reveals outbreaks of this type reported with oyster consumption from all over the world including different locales in the US.  Fortunately, I seem to remember the University of Louisiana did do a study and found that the use of Tabasco sauce was protective against infection (again, I apologize but I cannot find the reference either in my files or doing a PubMed search).

By this point, you may be wondering what any of this has to do with the lower extremity. Vibrio species, in particular V. vulnificus has the ability to cause rapidly progressive, frequently fatal necrotizing infections of the lower extremity in two ways.  First, direct inoculation of the organism into the soft tissues has been reported when marine water comes in contact with an open wound or if someone cuts themselves on a contaminated item in the marine environment (now, not only do I have to watch what I eat but I avoid swimming in the ocean too! ). But, the more common and deadly infection occurs after a patient ingests infected seafood and develops a Vibrio bacteremia and septicemia which then causes severe necrotizing skin and soft tissue infections.  A recent review by Horseman et al in the International Journal of Infectious Diseases (PubMed: http://www.ncbi.nlm.nih.gov/pubmed/21177133) reports a mortality rate exceeding 50%.  The authors opine that the antimicrobial regimen of choice is doxycycline combined with ceftazidime and aggressive surgical debridement.  Another study from just this year published by Tsai, et al in the American JBJS (PubMed: http://www.ncbi.nlm.nih.gov/pubmed/21266641) compares necrotizing infections by V. vulnificus and MRSA and finds the Vibrio infection progresses more rapidly and can be more deadly. They declare it to be a “surgical emergency”.

This case photograph was sent to me by Desmond Bell, DPM, CWS, a top podiatric wound authority and co-founder and Executive Director of the Save A Leg, Save a Life Foundation (SALSAL,  http://www.savealegsavealife.org/) I have known Des since his days as one of my students and have lectured a number of times at the SALSAL scientific meeting being held this year in Orlando October 27-30, 2011.  He received the photo courtesy of a colleague of his, Michael Baxley, MD.  The photograph shows a food wound in a patient who had developed Vibrio sepsis after ingesting oysters in coastal Alabama.  The patient fortunately survived the sepsis but now has skin wounds of varying severity on his hands, legs and feet.

 
Foot Infection Following Vibrio Bacteremia

 

Perhaps I should have written this post earlier in the summer season, before many of you went on vacation to the seashore…but then again, maybe not.

 

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Infection Control and Instrument Disinfection

July 25th, 2011 by Warren S. Joseph DPM FIDSA

This week I will be giving a talk to the Podiatric Assistants at the APMA National Meeting in Boston on the topic of office infection control.  I believe that this is an area which does not receive enough attention since it is far from “sexy” or cutting edge but is still important.  Last year I sat in on discussions by the Clinical Practices Committee of The American Podiatric Medical Association in an attempt to come up with some Guidelines for disinfection and sterilization of instruments for the podiatric physician.  This document, available online for members of APMA by searching the term “disinfection” in the Members Section at www.apma.org, incorporates information from the CDC document “Guidelines for Disinfection and Sterilization in Healthcare Facilities, 2008” also available online at http://www.cdc.gov/hicpac/pdf/guidelines/Disinfection_Nov_2008.pdf.  Much of the CDC document is not directly applicable to daily office practice, thus the need for the specialized Guidelines. 

In the APMA document we approached podiatric instrumentation much the same way as the dentist classify their instruments.  They are broken down into 3 categories:

Critical Instruments: These are any object that enters sterile tissue or the vascular system and therefore must be sterile because any contamination could transmit disease.  These would include any instrument used in a surgical procedure.  These instruments should be sterilized.

Semi-critical Instruments: These instruments contact non intact skin.  Examples would include tissue nippers or curettes used in debridement of an ulceration or incision and drainage of an abscess.  These devices require high level disinfection.

Noncritical Instruments: These come in contact with intact skin or nails. Virtually no risk has been documented for transmission of infection through noncritical instruments.  Examples would include nail nipper and burrs or handles used for debridement of keratotic lesions.  Low level disinfection can be used by intermediate level disinfection is recommended. 

Sterilization is the complete elimination of all vegetative bacteria, fungi and viruses along with any bacterial spores.  It can be achieved through a number of methods including the most commonly used steam/autoclave with a recommended minimum exposure of 30 minutes at 121° C.  Other techniques such as gas sterilization with ethylene oxide for moisture or pressure sensitive devices can also be used.  In the current document, based on FDA findings in dental offices, glass bead sterilization is not recommended. 

Disinfection has been broken down into 3 “levels”:

High level disinfection:  This is the complete elimination of all microorganisms on an instrument except for a small number of spores.  It is usually accomplished with a chemical such as glutaraldehyde.

Intermediate level disinfection: Destroys all vegetative bacteria, viruses and fungi but not bacterial spores.  This can be accomplished with phenolic compounds, iodophor, alcohol or chlorine.

Low level disinfection: Destroys all vegetative bacteria (except tuburcule bacilli) viruses and fungi but no spores. 

Finally, the APMA Guidelines discuss the need for various levels of disinfection with debridement procedures.  Debridement is broken down into manual, mechanical and dust extraction:

Manual: Instruments used in the manual debridement of nails such as nipper and curettes should be cleaned with intermediate level disinfectants.  Scalpel blades should not be reused and their handles can be treated as non-critical instruments.

Mechanical: Burrs should be thoroughly cleaned of any nail debris/dust and then treated with intermediate level disinfectants as noncritical instruments. 

Dust Exposure Precautions: The APMA recommends a dust extraction system or other safeguards to avoid exposure.  This may fall more under an OSHA recommendation than an infection control practice but I feel it is a critically overlooked precaution in many podiatric offices (as evidenced by the response I receive when I talk to Podiatric Assistants about this issue!).

This was just a superficial review of a complex topic but it is one of importance to all practices. These Guidelines are practical and quite “do-able”.  I remember sitting in on a lecture on office infection control at a Washington State Pod Med Assoc meeting a few years ago.  This talk, given by an infection control nurse working with a local county’s health department, basically required every single surface of the treatment room to be covered in disposable plastic drapes before each and every patient and thoroughly wiped down between patients.  It was far from practical and would have bankrupted the practice!  If we don’t follow basic infection control procedures as outlined in this APMA document who knows what agency will be telling us what to do next.

Posted in infection control, Infections | No Comments »

“PSEUDOMONA-PHOBIA”

May 16th, 2011 by Warren S. Joseph DPM FIDSA

For a number of years I have referred in my lectures to the word I have termed “Pseudomonaphobia”.  Basically, this is an irrational fear of the organism Pseudomonas aeruginosa (PA) when isolated from a culture of a wound in the foot.  I really believe that this arises in most Podiatrists during the residency interview process when, without fail they are asked by the interviewer “How would you treat a Pseudomonas infection in the foot?”  I remember being prepped for that question way back in 1981 when we were instructed that the correct response was “You use a combination of gentamicin and carbenicillin”.  Unfortunately, that was incorrect even back then since the more “current” schools were teaching their students to respond with a combination of tobramycin & ticarcillin, the so-called T&T therapy. (This may explain why I did not get my first choice of residency program!)  Fortunately, today the well prepared student should be able to recite about a dozen different, non-aminoglycoside options.  But, that is beside the point.  It really is a moot issue.  You see, despite the ability to readily culture the organism from lower extremity wounds, PA is RARELY a pathogen in lower extremity infections.   In fact, I would go as far as saying that about the only time PA should be empirically considered pathogenic is in a case of osteomyelitis following a puncture wound. 

Pseudomonas colonizing a heel wound

A number of randomized, controlled clinical trials have actually substantiated this viewpoint.  Most have looked at the clinical outcome of patients who grew PA from a wound/infection when treated empirically with an antibiotic that was ineffective against PA vs. one which had anti-pseudomonal activity. In this entry I will present 3 such trials.  

In 2002 Graham, et.al. published the results of the pivotal phase III trials comparing ertapenem to piperacillin/tazobactam for complicated skin and skin structure infections (PubMed link: http://www.ncbi.nlm.nih.gov/pubmed/12015692).  Of these two antibiotics ertapenem has no inherent anti-PA activity while pip/tazo does.  Despite this difference in spectrum, the positive clinical response in patients growing PA was 70% for ertapenem and 60% for pip/tazo.  In a very similar trial comparing the same two antibiotics specifically for diabetic foot infection, Lipsky et. al. had similar outcomes with a positive clinical response in 76.9% of patients on ertapenem vs. 70% for pip/tazo. (The SIDESTEP trial http://www.ncbi.nlm.nih.gov/pubmed/16291062).  More recently, in September 2010, Corey, et. al.  published the results of the clinical trials on the new anti-MRSA cephalosporin ceftaroline .  This drug has no inherent anti-PA activity yet there was a positive clinical response in 80% of the patients from which the organism was isolated.   

None of these trials are meant to show that the study drug had some previously undiscovered anti-PA activity.  They just point to the role of PA as a notorious colonizer of lower extremity wounds/infections. Nannini stated it quite succinctly in his review paper of ceftaroline (http://www.ncbi.nlm.nih.gov/pubmed?term=nannini%20ceftaroline):

“The demonstration of efficacy in patients with P. aeruginosa receiving ceftaroline, a pathogen against which ceftaroline has little activity, most probably reflects the presumptive role of P. aeruginosa as a colonizer rather than a true pathogen in many of these infections.”

Please do not misinterpret me.  I am not saying that PA is always a colonizer and is never pathogenic.  If this bug is found from a reliable, deep surgical culture, consideration should be given to covering it. However, this is a ubiquitous organism that has been found in tap water and on plants and vegetables.  Just culturing it from a superficial wound swab will lead the clinician to treat an organism that can most likely be handled with thorough debridement and topical therapy, with an anti-PA antibiotic that may be unnecessary.  This may increase resistance of the organism against these antibiotics so that they are not available for the next time…when we may really need them.

Posted in Antibiotics, Diabetic Foot, Infections, Osteomyelitis | No Comments »

Bugs and Drugs 2011 (Slide Show)

May 3rd, 2011 by Warren S. Joseph DPM FIDSA

With this entry onto the blog I am trying something new.  The IT team at Data Trace has been working on a way to post a PowerPoint slide show to the blog.  We believe it is now ready to go.  For this first PowerPoint, I am posting the lecture I gave at DFCON 2011 in Hollywood, CA back in late March.  The topic is “Bugs and Drugs 2011″.  As sometimes happens at that excellent meeting, I did not have enough time to go through the entire talk so, even back then, I offered to put the lecture up on my blog for viewing.  I hope you find the information on the slides interesting and informative.  If you have any questions about any content or see a subject on which you would like me to expound on this site, please let me know.

As always, comments on the site are welcomed.

Posted in Antibiotics, Diabetic Foot, Infections | No Comments »

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